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Accurate classification of gene expression data is crucial for disease diagnosis and drug discovery. However, gene expression data usually has a large number of features, which poses a challenge for accurate classification. In this paper, a novel feature selection method based on minimal redundancy maximal relevance (mRMR) and aquila optimizer is proposed, which introduces the mRMR method in the initialization stage of the population to generate excellent initial populations, effectively improve the quality of the population, and then, the using random opposition-based learning strategy to improve the diversity of aquila population and accelerate the convergence speed of the algorithm, and finally, introducing inertia weight in the position update formula in the late iteration of the aquila optimizer to avoid the algorithm falling into the local optimum and improve the algorithm's capability to find the optimum. In order to verify the effectiveness of the proposed method, ten real gene expression datasets are selected in this paper and compared with several meta-heuristic algorithms. Experimental results show that the proposed method is significantly superior to other meta-heuristic algorithms in terms of fitness value, classification accuracy and the number of selected features. Compared with the original aquila optimizer, the average classification accuracy of the proposed method on KNN and SVM classifiers is improved by 3.48–12.41% and 0.53–18.63% respectively. The proposed method significantly reduces the feature dimension of gene expression data, retains important features, and obtains higher classification accuracy, providing a new method and idea for feature selection of gene expression data. [ABSTRACT FROM AUTHOR]

In flowering plants, the predominant sexual morph is hermaphroditism, and the emergence of unisexuality is poorly understood. Using Cucumis melo (melon) as a model system, we explore the mechanisms driving sexual forms. We identify a spontaneous mutant exhibiting a transition from bisexual to unisexual male flower, and identify the causal mutation as a Harbinger transposon impairing the expression of Ethylene Insensitive 2 (CmEIN2) gene. Genetics and transcriptomic analysis reveal a dual role of CmEIN2 in both sex determination and fruit shape formation. Upon expression of CmACS11, EIN2 is recruited to repress the expression of the carpel inhibitor, CmWIP1. Subsequently, EIN2 is recruited to mediate stamina inhibition. Following the sex determination phase, EIN2 promotes fruit shape elongation. Genome-wide analysis reveals that Harbinger transposon mobilization is triggered by environmental cues, and integrates preferentially in active chromatin, particularly within promoter regions. Characterization of a large collection of melon germplasm points to active transpositions in the wild, compared to cultivated accessions. Our study underscores the association between chromatin dynamics and the temporal aspects of mobile genetic element insertions, providing valuable insights into plant adaptation and crop genome evolution. In flowering plants, hermaphroditism is widespread. Here the authors identified a transposon insertion that triggers plant sexual transition. This study highlights the role of transposons in plant adaptation and evolution. [ABSTRACT FROM AUTHOR]

The spike growth phase is critical for the establishment of fertile floret (grain) numbers in wheat (Triticum aestivum L.). Then, how to shorten the spike growth phase and increase grain number synergistically? Here, we showed high‐resolution analyses of floret primordia (FP) number, morphology and spike transcriptomes during the spike growth phase under three light regimens. The development of all FP in a spike could be divided into four distinct stages: differentiation (Stage I), differentiation and morphology development concurrently (Stage II), morphology development (Stage III), and polarization (Stage IV). Compared to the short photoperiod, the long photoperiod shortened spike growth and stimulated early flowering by shortening Stage III; however, this reduced assimilate accumulation, resulting in fertile floret loss. Interestingly, long photoperiod supplemented with red light shortened the time required to complete Stages I–II, then raised assimilates supply in the spike and promoted anther development before polarization initiation, thereby increasing fertile FP number during Stage III, and finally maintained fertile FP development during Stage IV until they became fertile florets via a predicted dynamic gene network. Our findings proposed a light regimen, critical stages and candidate regulators that achieved a shorter spike growth phase and a higher fertile floret number in wheat. Summary statement: A light regimen could achieve a 'shorter spike growth phase' and 'higher fertile floret number' in wheat by regulating gene expression, assimilate accumulation and morphology development in the critical stages of floret development. [ABSTRACT FROM AUTHOR]

High temperature around flowering has a serious impact on the growth and development of maize. However, few maize genes related to flowering under heat stress have been confirmed, and the regulatory mechanism is unclear. To reveal the molecular mechanism of heat tolerance in maize, two maize hybrids, ZD309 and XY335, with different heat resistance, were selected to perform transcriptome and metabolomics analysis at the flowering stage under heat stress. In ZD309, 314 up-regulated and 463 down-regulated differentially expressed genes (DEGs) were detected, while 168 up-regulated and 119 down-regulated DEGs were identified in XY335. By comparing the differential gene expression patterns of ZD309 and XY335, we found the "frontloaded" genes which were less up-regulated in heat-tolerant maize during high temperature stress. They included heat tolerance genes, which may react faster at the protein level to provide resilience to instantaneous heat stress. A total of 1062 metabolites were identified via metabolomics analysis. Lipids, saccharides, and flavonoids were found to be differentially expressed under heat stress, indicating these metabolites' response to high temperature. Our study will contribute to the identification of heat tolerance genes in maize, therefore contributing to the breeding of heat-tolerant maize varieties. [ABSTRACT FROM AUTHOR]

Pilocytic astrocytoma (PA) is the most common primary brain tumor in children and adolescents. Treatment strategy largely depends on its key genes and molecular mutations. This study aimed to identify potential biomarkers of PA closely related to its prognosis. The gene expression profiles (series numbers GSE50161, GSE66354, and GSE86574) of PA and normal brain tissues were downloaded from the Gene Expression Omnibus database. The Gene Expression Omnibus2R was used to identify differentially expressed genes. The overlapping differentially expressed genes were subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database. A protein-protein interaction network was constructed using Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape. The Gene Expression Profiling Interactive Analysis 2 (GEPIA2) tool analyzed the impact of hub genes on PA prognosis based on the Kaplan–Meier curves. Compared with normal brain tissues (n = 36), a total of 37 upregulated and 144 downregulated genes were identified in PA (n = 40). In the protein-protein interaction network construction and GEPIA2 survival analysis, 2 of the top 10 hub genes were significantly associated with decreased overall survival of PA patients, namely Gamma-aminobutyric acid A receptor alpha 2 (hazard ratio = 2.8, P < 0.01) and regulating synaptic membrane exocytosis protein 1) (hazard ratio = 3.2, P < 0.01). This bioinformatics analysis reveals that low expression of Gamma-aminobutyric acid A receptor alpha 2 and regulating synaptic membrane exocytosis protein 1 is associated with a favorable prognosis for PA patients. These 2 hub genes could be novel biomarkers for prognosis assessment, furthermore a key element for treatment decisions in the future. [ABSTRACT FROM AUTHOR]

To analyse the pathogenic genes and mutations of a family with hereditary deafness. We recruited a three-generation family with NSHL. A detailed medical history inquiry and related examinations were performed. Next-generation sequencing (NGS) was used to confirm the gene mutation in the proband, and Sanger sequencing was used for verification. The effect of the WFS1 mutation on the function and structure of the wolframin protein was predicted by multiple computational software. From the Gene Expression Omnibus (GEO) database, we obtained GSE40585 dataset and performed enrichment analyses. The family clinically manifested as autosomal dominant NSHL. A novel WFS1 c.2421C>G (p.Ser807Arg) mutation was identified in four affected individuals in the pedigree. The p.Ser807Arg mutation is a highly conserved residue and causes an increase in protein stability. It had an important influence on not only amino acid size, charge and hydrophobicity but also protein intermolecular hydrogen bonding and spatial structure. There were differentially expressed genes (DEGs) in GSE40585 dataset. Enrichment analysis revealed that DEGs mainly functioned in amino acid metabolism, signal transduction and dephosphorylation. We reported a novel mutation c.2421C>G (p.Ser807Arg in WFS1. This study expands the mutation spectrum of WFS1. [ABSTRACT FROM AUTHOR]

CYP3A4, CYP3A5, and CYP3A7, which are located in a multigene locus (CYP3A), play crucial roles in drug metabolism. To understand the highly variable hepatic expression of CYP3As, regulatory network analyses have focused on transcription factors (TFs). Since long non-coding RNAs (lncRNAs) likely contribute to such networks, we assessed the regulatory effects of both TFs and lncRNAs on CYP3A expression in the human liver and small intestine, main organs of CYP3A expression. Using weighted gene co-expression network analysis (WGCNA) of GTEx v8 RNA expression data and multiple stepwise regression analysis, we constructed TF-lncRNA-CYP3A co-expression networks. Multiple lncRNAs and TFs displayed robust associations with CYP3A expression that differed between liver and small intestines (LINC02499, HNF4A-AS1, AC027682.6, LOC102724153, and RP11-503C24.6), indicating that lncRNAs contribute to variance in CYP3A expression in both organs. Of these, HNF4A-AS1 had been experimentally demonstrated to affect CYP3A expression. Incorporating ncRNAs into CYP3A expression regulatory network revealed additional candidate TFs associated with CYP3A expression. These results serve as a guide for experimental studies on lncRNA-TF regulation of CYP3A expression in the liver and small intestines. [ABSTRACT FROM AUTHOR]

APETALA2/Ethylene Responsive Factor (AP2/ERF) family plays important roles in reproductive development, stress responses and hormone responses in plants. However, AP2/ERF family has not been systematically studied in Dendrobium catenatum. In this study, 120 AP2/ERF family members were identified for the first time in D. catenatum, which were divided into four groups (AP2, RAV, ERF and DREB subfamily) according to phylogenetic analysis. Gene structures and conserved motif analysis showed that each DcAP2/ERF family gene contained at least one AP2 domain, and the distribution of motifs varied among subfamilies. Cis-element analysis indicated that DcAP2/ERF genes contained abundant cis-elements related to hormone signaling and stress response. To further identify potential genes involved in drought stress, 12 genes were selected to detect their expression under drought treatment through qRT-PCR analysis and DcAP2/ERF#96, a nuclear localized ethylene-responsive transcription factor, showed a strong response to PEG treatment. Overexpression of DcAP2/ERF#96 in Arabidopsis showed sensitivity to ABA. Molecular, biochemical and genetic assays indicated that DcAP2ERF#96 interacts with DREB2A and directly inhibits the expression of P5CS1 in response to the ABA signal. Taken together, our study provided a molecular basis for the intensive study of DcAP2/ERF genes and revealed the biological function of DcAP2ERF#96 involved in the ABA signal. [ABSTRACT FROM AUTHOR]

Cardiovascular and cerebrovascular diseases are the leading causes of death worldwide and interact closely with each other. Danhong Injection (DHI) is a widely used preparation for the co-treatment of brain and heart diseases (CTBH). However, the underlying molecular endotype mechanisms of DHI in the CTBH remain unclear. To elucidate the underlying endotype mechanisms of DHI in the CTBH. In this study, we proposed a modular-based disease and drug-integrated analysis (MDDIA) strategy for elucidating the systematic CTBH mechanisms of DHI using high-throughput transcriptome-wide sequencing datasets of DHI in the treatment of patients with stable angina pectoris (SAP) and cerebral infarction (CI). First, we identified drug-targeted modules of DHI and disease modules of SAP and CI based on the gene co-expression networks of DHI therapy and the protein–protein interaction networks of diseases. Moreover, module proximity-based topological analyses were applied to screen CTBH co-module pairs and driver genes of DHI. At the same time, the representative driver genes were validated via in vitro experiments on hypoxia/reoxygenation-related cardiomyocytes and neuronal cell lines of H9C2 and HT22. Seven drug-targeted modules of DHI and three disease modules of SAP and CI were identified by co-expression networks. Five modes of modular relationships between the drug and disease modules were distinguished by module proximity-based topological analyses. Moreover, 13 targeted module pairs and 17 driver genes associated with DHI in the CTBH were also screened. Finally, the representative driver genes AKT1 , EDN1 , and RHO were validated by in vitro experiments. This study, based on clinical sequencing data and modular topological analyses, integrated diseases and drug targets. The CTBH mechanism of DHI may involve the altered expression of certain driver genes (SRC, STAT3, EDN1, CYP1A1, RHO, RELA) through various enriched pathways, including the Wnt signaling pathway. [Display omitted] • A modular-based disease and drug-integrated analysis strategy was proposed to reveal the co-treatment mechanisms of diseases. • Drug-targeted modules of Danhong injection and disease modules of stable angina pectoris and cerebral infarction were identified. • Co-module pairs and drive genes of Danhong injection were screened using proximity-based topological analyses. • The representative drive genes were validated by in vitro experiments. • The endotype driven co-module mechanisms of Danhong Injection for cardiovascular and cerebrovascular diseases were explained. [ABSTRACT FROM AUTHOR]

Background: Acetabular labral tear is one of the contributing factors to early hip osteoarthritis. Patients with symptomatic labral tears may require surgical treatment, and labral reconstruction is indicated in cases of irreparable tears. Purpose: The purpose of the study was to construct the bone morphogenic protein 2 (BMP-2) electrospun scaffold for acetabular labral reconstruction and analyze the composition of the labrum and the influence of collagen fiber distribution in regenerated tissue on the biomechanical properties of labrum. Study Design: Controlled laboratory study. Methods: Eighteen mature male miniature pigs were selected for labral reconstruction in vivo. The animals were divided into 3 groups, including the autologous tendon group (T group), dopamine/polylactic acid–polyethylene glycol (PELA) electrospun group (DP group), and dopamine/PELA electrospun/BMP-2 group (DPB group), and the native labra were used as the control group. The microstructure of the reconstructed labrum was analyzed by scanning electron microscopy. Histologic and immunohistochemistry sections were used to evaluate the composition and structure of reconstructed labrum. The related gene expression was tested via quantitative reverse transcriptase–polymerase chain reaction test. The compressive and tensile properties of tissues were evaluated using the elasticity test device. Results: Hematoxylin and eosin staining showed that the DP group and the T group were mainly composed of fibroblasts. The alignment of fibers was irregular. In the DPB group, the reconstructed tissues were composed of fibroblasts and chondrocytes, with parallel fibers and denser structure. The native labrum was composed of a large number of fibroblasts, which were arranged orderly and parallel, and there was almost no vascular proliferation. Under scanning electron microscopy, the reconstructed tissue of the DBP group was more similar to the native labral structure, forming a denser, clear-layered collagen fibrous structure, while the fiber alignment of the DP and T groups was irregular. The contents of type I, II, and III collagen (COL1, COL2, and COL3, respectively) were upregulated in labrum reconstructed with the DPB scaffold, while the gene expressions did not increase in the DP and T groups. The tensile and compressive properties of the implants in the DPB group were significantly enhanced. Conclusion: BMP-2 modified electrospun scaffold promotes collagen regeneration and osteogenic differentiation and is associated with better biomechanical performance of the reconstructed labrum. Clinical Relevance: This study demonstrated that BMP-2 modified electrospun scaffold could induce the regeneration of collagen and osteogenic differentiation and provide better biomechanical performance in labral reconstruction. This scaffold could be used in clinical practice after further improvement. [ABSTRACT FROM AUTHOR]

In order to study the effects of exogenous GA3 and IAA on tobacco growth regulation and chemical composition, the mechanism of exogenous hormones and the optimal hormone concentration were explored based on hormone and gene levels-explore. Taking the flue, cured tobacco variety NC71 as the experimental material, this paper set different concentration treatments of exogenous hormones to detect the changes of plant height, dry matter accumulation, hormone content, related gene expression and tobacco leaf quality. The results showed that exogenous GA3 could significantly increase the plant height and pitch of flue, cured tobacco, while the relative increase of exogenous IAA was less, and the dry matter quality of tobacco plants increased with the increase of GA3 concentration. Spraying different concentrations of exogenous GA3 and IAA increased the content of GA3 and IAA in shoot tip and reduced the content of ABA and the effect of 150 mg/ L was the most obvious, the exogenous GA3 of 100 mg/ L and the exogenous IAA of 10 mg/ L were the second exogenous. GA3 significantly reduced the expression of GAI1 gene in tobacco, and IAA also reduced the relative expression of GAI gene, but the effect was relatively weak. The content of total sugar, reducing sugar and potassium in tobacco leaves sprayed with exogenous hormones increased, while the contents of total nitrogen, nicotine and chlorine decreased, and potassium in the condition of 100 mg/ L exogenous GA3 combined with IAA. The ratio of chlorine to sugar and alkali was the highest, and the quality was better, so 100 mg/ L exogenous GA3 and 10 mg/ L exogenous IAA were sprayed 15 d after transplanting according to the principle of lessness. These results provided a basis for the application of exogenous growth regulators to flue, cured tobacco in the central part of Henan province tobacco area. [ABSTRACT FROM AUTHOR]

FOXA1 functions as a pioneer factor of transcriptional regulation that binds to specific sites in the chromatin and recruits other transcription factors, promoting the initiation of gene transcription and mediating the regulation of downstream target gene expression. FOXA1 was reported to facilitate or reprogram ERα binding, thus playing a key function in breast cancer progression. Our previous results indicated that the O-linked N-acetylgalactosamine (O-GalNAc) modification of FOXA1 plays a potentially significant role in the ERα transcription network. However, further investigations are needed to identify the specific mechanism of modification and the specific glycosylation sites on FOXA1. In this study, we first suggested that FOXA1 could be O-GalNAcylated by ppGalNAc-T2 in vitro. By dividing and expressing recombinant FOXA1 as three segments, two O-GalNAcylation sites were found on FOXA1, both located at the C-terminal of the protein. Then, synthesized peptides, including the predicted O-GalNAc sites in the C-terminus of FOXA1, were used in a vitro reaction, and peptides mutated at the predicted O-GalNAc sites were employed as controls. Through an ESI-MS assay, S354 and S355 were identified as probable O-GalNAcylation sites on FOXA1. Additionally, we performed ESI-ETD-MS/MS analysis of the full-length O-GalNAcylated FOXA1 protein and identified S355 as the O-GalNAc modification site on FOXA1, consistent with the peptide reaction. In conclusion, our results demonstrated that FOXA1 can be O-GalNAcylated by ppGalNAc-T2 at S355 in vitro. These results will provide new insights for studying the role of O-GalNAcylation in the development of breast cancer. • Nuclear transcription factor FOXA1, which plays a key function in tumor progression was confirmed to be O-GalNAcylated by ppGalNAc-T2 in vitro. • By dividing and expressing recombinant FOXA1 as three segments, two O-GalNAcylation sites were found on FOXA1 by HPLC and mass ESI-MS, both located at the C-terminal of the protein. • ESI-ETD-MS/MS analysis of the full-length in vitro O-GalNAcylated FOXA1 protein identified S355 as the O-GalNAc modification site on FOXA1. [ABSTRACT FROM AUTHOR]

Phenolic compounds have various nutritional and functional properties, especially antioxidant activity. The objective of this study was to explore the relationship between the phenolic compound accumulation, antioxidant property and gene expression during maize kernel development. In this study, we explored the effects of developmental stage on the accumulation of phenolic compounds and their antioxidant activities. The expression levels of genes involved in phenolic biosynthesis were also studied. The results showed that the total phenolic content (TPC) and total anthocyanin content (TAC) were gradually increased from 15 to 48 days after pollination (DAP), whereas the total flavonoid content (TFC) decreased continuously. The antioxidant activity of maize kernels was increased gradually and positively associated with TPC. ZmCHS s in flavonoid biosynthetic pathway played important roles for total flavonoid accumulation at both early and later development stages. The expression pattern of ZmANS corresponded to the accumulation of total anthocyanin during kernel development. These results revealed that developmental stage affected the accumulation of different phenolic compounds, antioxidant activity and related gene expression. The antioxidant activity of maize kernels was dependent on the total phenolic accumulation which was related to the expression profiles of the genes participated in phenolic synthesis. Image 1 • Growth stage affects maize phenolic compound accumulation and antioxidant activity. • The antioxidant activity is positively and significantly correlated with TPC. • Two ZmCHS s are correlated with the total flavonoid accumulation. • ZmANS play important role in anthocyanin biosynthesis during kernel development. • Phenolic bio-fortification in maize may enhance health benefits. [ABSTRACT FROM AUTHOR]

Poria cocos (Schw.) Wolf (Polyporaceae, P.cocos), which is born on the pine root, has a history of more than two thousand years of medicine in China. P.cocos was first recorded in the Shennong's Herbal Classic, studies have proved its lipid-lowering effect. The aim of study was to investigate the underlying mechanism of P.cocos extract on hyperlipidemia. Male Sprague-Dawley (SD) rats aged 9–12 weeks were intraperitoneally (IP) injected with Triton-WR 1339 to establish an acute hyperlipidemia model. At 0 h and 20 h after the model was established, low and high doses of P.cocos extract or simvastatin were given twice. After 48 h, the rats were sacrificed, and liver and serum samples were collected for analysis. The cell model was constructed by treating L02 cells with 1% fat emulsion-10% FBS–RPMI 1640 medium for 48 h. At the same time, low and high doses of P.cocos extract and simvastatin were administered. Oil red O staining was used to evaluate the lipid accumulation in the cells, and H&E staining was used to evaluate the liver lesions of rats. Real-time quantitative PCR and western blotting were used to detect the expressions of lipid metabolism-related genes. P.cocos extract relieved lipid accumulation in vitro and alleviated hyperlipidemia in vivo. Both gene and protein expressions of peroxisome proliferator-activated receptor α (PPARα) were shown to be up-regulated by P.cocos extract. Additionally, P.cocos extract down-regulated the expressions of fatty acid synthesis-related genes sterol regulatory element-binding protein-1 (SREBP-1), Acetyl-CoA Carboxylase 1 (ACC1) and fatty acid synthase (FAS), while up-regulated the expressions of cholesterol metabolism-related genes liver X receptor-α (LXRα), ATP-binding cassette transporter A1 (ABCA1), cholesterol 7alpha-hydroxylase (CYP7A1) and low density lipoprotein receptor (LDLR), which were reversed by the treatment with the PPARα inhibitor GW6471. P.cocos extract ameliorates hyperlipidemia and lipid accumulation by regulating cholesterol homeostasis in hepatocytes through PPARα pathway. This study provides evidence that supplementation with P.cocos extract could be a potential strategy for the treatment of hyperlipidemia. [Display omitted] • P.cocos extract alleviated hyperlipidemia in vivo and in vitro. • P.cocos extract regulated lipid metabolism in hepatocytes. • P.cocos extract regulated lipid metabolism in hepatocytes via PPARα pathway. • PPARα inhibitor GW6471 attenuated the lipid-lowering effect of P.cocos extract. • Triterpenes were the main active ingredients in the lipid-lowering P.cocos extract. [ABSTRACT FROM AUTHOR]

Panax notoginseng (Bruk.) FH Chen is a valuable traditional herb in China, with saponins being the main medicinal components in its roots. However, leaf diseases are a major factor limiting growth and production of P. notoginseng. Melatonin is a ubiquitous signaling molecule associated with abiotic stress resistance. In this study, we investigated the role of melatonin in leaf disease resistance of P. notoginseng in field conditions. Additionally, saponin concentrations were analyzed to evaluate the suitability of melatonin use in agricultural practice. Our results showed that exogenous application of melatonin promoted the endogenous phytomelatonin accumulation via upregulation of genes involved in its biosynthesis. The application of 10 μM melatonin decreased the incidence of leaf diseases (gray mold, round spot, and black spot) by about 40% compared with the solvent control, which might have been due to the increased expression of genes associated with immunity and disease resistance. Furthermore, concentrations of saponins and expression of their biosynthesis-related genes were significantly increased by melatonin. Taken together, the data presented here suggested that melatonin could be used in agricultural management of P. notoginseng because it increased leaf disease resistance and biosynthesis of saponins. [ABSTRACT FROM AUTHOR]